Society for Maternal-Fetal Medicine

View all recommendations from this society

May 1, 2019

Don’t test women for MTHFR mutations.

MTHFR is responsible for the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. Genetic variant C677T and A1286C have been associated with a mild decrease in enzymatic activity, which in the setting of reduced folate levels has been found to be a risk factor for hyperhomocysteinemia. Although hyperhomocysteinemia is a risk factor for cardiovascular disease and venous thrombosis, its cause is multifactorial and independent of the MTHFR genotype, even in homozygotic individuals. Despite earlier (mostly case control) studies that found an association between the MTHFR genotype and adverse outcomes, recent studies of more robust design have not replicated these findings. Due to the lack of evidence associating genotype independently with thrombosis, recurrent pregnancy loss, or other adverse pregnancy outcomes, MTHFR genotyping should not be ordered as part of a workup for thrombophilia.


These items are provided solely for informational purposes and are not intended as a substitute for consultation with a medical professional. Patients with any specific questions about the items on this list or their individual situation should consult their physician.

How The List Was Created

As a national medical specialty society, the Society for Maternal-Fetal Medicine relies on the input of any number of its committees in the development of various documents. In the case of the items included in this list, the Publications Committee reviewed the literature and evidence from SMFM’s published documents for possible topics. For SMFM’s first set of five recommendations a sub-group of the Committee initially developed a list of 10 items that the Committee then ranked for the top five with input and suggestions by the Society’s Executive Committee. For SMFM’s second set of recommendations, the sub-group of the Committee developed a list of 12 items that the Committee then ranked for the top five, again soliciting input and suggestions by the Society’s Executive Committee. For SMFM’s third set of five recommendations, the sub-group of the Publications Committee developed a list of 10 items that the Committee ranked for the top five, again soliciting input and suggestions by the Society’s Executive Committee. The final lists have been reviewed and approved by the Society’s Document Review Committee and Executive Committee.

SMFM’s disclosure and conflict of interest policy can be found at www.smfm.org

Sources

Inherited thrombophilias in pregnancy. ACOG Practice Bulletin No. 197. American College of Obstetricians and Gynecologists. Obstet Gynecol 2018;132:e18—34.

Hickey SE, Curry CJ, Toriello HV. ACMG Practice Guideline: lack of evidence
for MTHFR polymorphism testing. Genet Med. 2013 Feb;15(2):153-6.

Baglin T, Gray E, Greaves M, et al. Clinical guidelines for testing for heritable thrombophilia. Br J Haematol 2010;149:209–220.